Meta-analysis and transcriptomic analysis reveal that NKRF and ZBTB17 regulate the NF-κB signaling pathway, contributing to the shared molecular mechanisms of Alzheimer's disease and atherosclerosis.

INTRODUCTION: Alzheimer's disease (AD) and atherosclerosis (AS) are widespread diseases predominantly observed in the elderly population. Despite their prevalence, the underlying molecular interconnections between these two conditions are not well understood. METHODS: Utilizing meta-analysis, bioinformatics methodologies, and the GEO database, we systematically analyzed transcriptome data to pinpoint key genes concurrently differentially expressed in AD and AS. Our experimental validations in mouse models highlighted the prominence of two genes, NKRF (NF-κB-repressing factor) and ZBTB17 (MYC-interacting zinc-finger protein 1). RESULTS: These genes appear to influence the progression of both AD and AS by modulating the NF-κB signaling pathway, as confirmed through subsequent in vitro and in vivo studies. CONCLUSIONS: This research uncovers a novel shared molecular pathway between AD and AS, underscoring the significant roles of NKRF and ZBTB17 in the pathogenesis of these disorders.

Machine learning models to predict submucosal invasion in early gastric cancer based on endoscopy features and standardized color metrics.

Conventional endoscopy is widely used in the diagnosis of early gastric cancers (EGCs), but the graphical features were loosely defined and dependent on endoscopists' experience. We aim to establish a more accurate predictive model for infiltration depth of early gastric cancer including a standardized colorimetric system, which demonstrates promising clinical implication. A retrospective study of 718 EGC cases was performed. Clinical and pathological characteristics were included, and Commission Internationale de l'Eclariage (CIE) standard colorimetric system was used to evaluate the chromaticity of lesions. The predicting models were established in the derivation set using multivariate backward stepwise logistic regression, decision tree model, and random forest model. Logistic regression shows location, macroscopic type, length, marked margin elevation, WLI color difference and histological type are factors significantly independently associated with infiltration depth. In the decision tree model, margin elevation, lesion located in the lower 1/3 part, WLI a*color value, b*color value, and abnormal thickness in enhanced CT were selected, which achieved an AUROC of 0.810. A random forest model was established presenting the importance of each feature with an accuracy of 0.80, and an AUROC of 0.844. Quantified color metrics can improve the diagnostic precision in the invasion depth of EGC. We have developed a nomogram model using logistic regression and machine learning algorithms were also explored, which turned out to be helpful in decision-making progress.

Serum proteomic profiling of precancerous gastric lesions and early gastric cancer reveals signatures associated with systemic inflammatory response and metaplastic differentiation.

The noninvasive detection technique using serum for large-scale screening is useful for the early diagnosis of gastric cancer (GC). Herein, we employed liquid chromatography mass spectrometry to determine the serum proteome signatures and related pathways in individuals with gastric precancerous (pre-GC) lesions and GC and explore the effect of Helicobacter pylori (H. pylori) infection. Differentially expressed proteins in GC and pre-GC compared with non-atrophic gastritis (NAG) group were identified. APOA4, a protein associated with metaplastic differentiation, and COMP, an extracellular matrix protein, were increased in the serum of patients with pre-GC lesions and GC. In addition, several inflammation-associated proteins, such as component C3, were decreased in the GC and pre-GC groups, which highlight a tendency for the inflammatory response to converge at the gastric lesion site during the GC cascade. Moreover, the abundance of proteins associated with oxidant detoxification was higher in the GC group compared with that in the NAG group, and these proteins were also increased in the serum of the H. pylori-positive GC group compared with that in the H. pylori-negative GC patients, reflecting the importance of oxidative stress pathways in H. pylori infection. Collectively, the findings of this study highlight pathways that play important roles in GC progression, and may provide potential diagnostic biomarkers for the detection of pre-GC lesions.

Inhibition of Verticillium Wilt in Cotton through the Application of Pseudomonas aeruginosa ZL6 Derived from Fermentation Residue of Kitchen Waste.

To isolate and analyze bacteria with Verticillium wilt-resistant properties from the fermentation residue of kitchen wastes, as well as explore their potential for new applications of the residue. A total of six bacterial strains exhibiting Verticillium wilt-resistant capabilities were isolated from the biogas residue of kitchen waste fermentation. Using a polyphasic approach, strain ZL6, which displayed the highest antagonistic activity against cotton Verticillium wilt, was identified as belonging to the Pseudomonas aeruginosa. Bioassay results demonstrated that this strain possessed robust antagonistic abilities, effectively inhibiting V. dahliae spore germination and mycelial growth. Furthermore, P. aeruginosa ZL6 exhibited high temperature resistance (42o C), nitrogen fixation, and phosphorus removal activities. Pot experiments revealed that P. aeruginosa ZL6 fermentation broth treatment achieved a 47.72% biological control effect compared to the control group. Through activity tracking and protein mass spectrometry identification, a neutral metalloproteinase (Nml) was hypothesized as the main virulence factor. The mutant strain ZL6ΔNml exhibited a significant reduction in its ability to inhibit cotton Verticillium wilt compared to the strain P. aeruginosa ZL6. While the inhibitory activities could be partially restored by a complementation of nml gene in the mutant strain ZL6CMΔNml. This research provides a theoretical foundation for the future development and application of biogas residue as biocontrol agents against Verticillium wilt and as biological preservatives for agricultural products. Additionally, this study presents a novel approach for mitigating the substantial amount of biogas residue generated from kitchen waste fermentation.

Prioritizing Organic Pollutants for Shale Gas Exploitation: Life Cycle Environmental Risk Assessments in China and the US.

Environmental impacts associated with shale gas exploitation have been historically underestimated due to neglecting to account for the production or the release of end-of-pipe organic pollutants. Here, we assessed the environmental impacts of shale gas production in China and the United States using life cycle assessment. Through data mining, we compiled literature information on organic pollutants in flowback and produced water (FPW), followed by assessments using USEtox to evaluate end-of-pipe risks. Results were incorporated to reveal the life cycle risks associated with shale gas exploitation in both countries. China exhibited higher environmental impacts than the US during the production phase. Substantially different types of organic compounds were observed in the FPW between two countries. Human carcinogenic and ecological toxicity attributed to organics in FPW was 3 orders of magnitude higher than that during the production phase in the US. Conversely, in China, end-of-pipe organics accounted for approximately 52%, 1%, and 47% of the overall human carcinogenic, noncarcinogenic, and ecological impacts, respectively. This may be partially limited by the quantitative data available. While uncertainties exist associated with data availability, our study highlights the significance of integrating impacts from shale gas production to end-of-pipe pollution for comprehensive environmental risk assessments.

Mogrol-Mediated enhancement of radiotherapy sensitivity in Non-Small cell lung cancer: A mechanistic study.

OBJECTIVE: Investigate Mogrol's impact on NSCLC radiosensitivity and underlying mechanisms using various methods including assays, bioinformatics, and xenograft models. METHODS: CCK-8, clonogenic, flow cytometry, TUNEL, and Western blot assays evaluated Mogrol and radiation effects on NSCLC viability and apoptosis. USP22 expression in NSCLC patient tissues was determined using RT-qPCR and Western blot. A xenograft model validated Mogrol's effects on tumor growth. RESULTS: Bioinformatics identified four ubiquitin-specific proteases, including USP22, in NSCLC. Kaplan-Meier analysis confirmed USP22's value in lung cancer survival. HPA database indicated higher USP22 expression in lung cancer tissues. GO and KEGG analysis implicated ERK1/2 in NSCLC progression, and molecular docking showed stability between Mogrol and ERK1/2. Further in vivo and in vitro experiments have demonstrated that Mogrol enhances the inhibitory effect of radiation on NSCLC cell viability and clonogenic capacity. Cell viability and clonogenic capacity are reduced by more than 50%, and an increase in cellular apoptosis is observed, with apoptotic levels reaching 10%. USP22 expression was significantly elevated in NSCLC tissues, particularly in radiotherapy-resistant patients. Mogrol downregulated USP22 expression by inhibiting the ERK/CREB pathway, lowering COX2 expression. Mogrol also enhanced radiation's inhibition of tumor growth in mice. CONCLUSION: Mogrol enhances NSCLC radiosensitivity by downregulating USP22 via the ERK/CREB pathway, leading to reduced COX2 expression.

Adsorption Characteristics of Ball Milling-Modified Chinese Medicine Residue Biochar Toward Quercetin.

Using traditional Chinese medicine residues as raw materials, different biochars (BC) were prepared through oxygen-limited pyrolysis at 300 °C, 500 °C, and 700 °C, and BC was ball-milled to produce ball-milled biochar (BMC). Using these adsorbents to adsorb the allelopathic autotoxic substance quercetin. The physical and chemical properties of various biochars derived from traditional Chinese medicine residues were characterized using the Brunauer-Emmett-Teller-N2 surface areas (BET), scanning electron microscopy (SEM), Fourier transform IR spectroscopy (FTIR), X-ray diffraction (XRD), and Raman spectroscopy (Raman). The study investigated the effects of the initial pH value, different humic acid concentrations, and multiple adsorption-desorption experiments on the removal of quercetin from the solution. The article discusses the adsorption mechanism of quercetin in solution by biochar from a traditional Chinese medicine residue, based on the results of adsorption kinetics and adsorption isotherm fitting. The findings indicate that increasing the pyrolysis temperature reduces the oxygen-containing functional groups of BC, enhances the aromaticity, and stabilizes the carbon structure. The pore structure of BMC becomes more complex after ball milling, which increases the number of oxygen-containing functional groups on the surface. Among the samples tested, BMC700 exhibits the best adsorption performance, with an adsorption capacity of 293.3 mg·g-1 at 318 K. The adsorption process of quercetin by BMC700 follows the pseudo-second-order kinetic model and the Freundlich adsorption isotherm model. The process is primarily a form of multimolecular layer adsorption. Its mechanism involves the pore-filling effect, hydrogen-bonding interaction, electrostatic interaction, and π-π coexistence, as well as the yoke effect. Additionally, they are highly recyclable and show promise in addressing continuous cropping issues.

Exploring the diagnostic value of blood circular RNA in atherosclerotic cardiovascular diseases by integrating bioinformatics and evidence-based medicine meta-analysis.

This meta-analysis aimed to investigate the diagnostic value of blood circular RNA (circRNA) in atherosclerotic cardiovascular diseases (AS). Using bioinformatics and evidence-based medicine, we identified circ_0001900 as a potential biomarker for diagnosing AS-related cardiovascular diseases. Bioinformatics analysis indicated that circ_0001900 may participate in AS progression by regulating lipid and atherosclerosis-related genes on the MAPK1/3, SRC, TRAF6, and STAT3 signaling pathways. In vivo results showed that circ_0001900 was significantly up-regulated in AS mouse and AS patients' peripheral blood (PB), serum, serum serum extracellular vesicles (EVs), and peripheral blood mononuclear cells (PBMCs), with good diagnostic efficacy as evaluated by ROC curve analysis. Circ_0001900 knockout inhibited AS progression, which may be related to the regulation of these signaling pathways. These findings suggest that circ_0001900 may serve as a potential diagnostic and therapeutic target for AS-related cardiovascular diseases.

Smartphone-Enabled Fluorescence and Colorimetric Platform for the On-Site Detection of Hg2+ and Cl- Based on the Au/Cu/Ti3C2 Nanosheets.

Smartphone-assisted fluorescence and colorimetric methods for the on-site detection of Hg2+ and Cl- were established based on the oxidase-like activity of the Au-Hg alloy on the surface of Au/Cu/Ti3C2 NSs. The Au nanoparticles (NPs) were constructed via in-situ growth on the surface of Cu/Ti3C2 NSs and characterized by different characterization techniques. After the addition of Hg2+, the formation of Hg-Au alloys could promote the oxidization of o-phenylenediamine (OPD) to generate a new fluorescence emission peak of 2,3-diaminopenazine (ADP) at 570 nm. Therefore, a turn-on fluorescence method for the detection of Hg2+ was established. As the addition of Cl- can influence the fluorescence of ADP, the fluorescence intensity was constantly quenched to achieve the continuous quantitative detection of Cl-. Therefore, a turn-off fluorescence method for the detection of Cl- was established. This method had good linear ranges for the detection of Hg2+ and Cl- in 8.0-200.0 nM and 5.0-350.0 µM, with a detection limit of 0.8 nM and 27 nM, respectively. Depending on the color change with the detection of Hg2+ and Cl-, a convenient on-site colorimetric method for an analysis of Hg2+ and Cl- was achieved by using digital images combined with smartphones (color recognizers). The digital picture sensor could analyze RGB values in concentrations of Hg2+ or Cl- via a smartphone app. In summary, the proposed Au/Cu/Ti3C2 NSs-based method provided a novel and more comprehensive application for environmental monitoring.

Facile Synthesis of MXene-Ti3C2/Co Nanosheet Hydrogel Sensor with the Assistance of a Smartphone for On-Site Monitoring of Glucose in Beverages.

A one-step cobaltous chloride (CoCl2) molten salt method was employed to prepare multilayer MXene-Ti3C2/Co materials with further ultrasonic treatment to acquire single-layer MXene-Ti3C2/Co nanosheets (NSs). MXene-Ti3C2/Co NSs were characterized, and their enzyme-like activities were investigated. Under the catalysis of MXene-Ti3C2/Co NSs, 3,3',5,5'-tetramethylbenzidine (TMB) could be oxidized by H2O2, with the color changing from colorless to blue. The affinity of MXene-Ti3C2/Co NSs to H2O2 and TMB was better than that of nanozymes reported in previous studies. The MXene-Ti3C2/Co NSs were used for the colorimetric determination of H2O2/glucose, with limits of detection (LODs) of 0.033 mM and 1.7 µM, respectively. MXene-Ti3C2/Co NSs embedded in sodium alginate (SA) hydrogel were used to construct a sensor platform. The digital pictures combined with a smartphone-installed app (color recognizer) could be used to analyze RGB values for colorimetric detection of glucose in beverages. This point-of-care testing platform has the advantages of cost-effectiveness and good transferability, with the potential to realize quick, intelligent and on-site detection.

Sunlight Significantly Enhances Soil Denitrification via an Interfacial Biophotoelectrochemical Pathway.

Denitrification is an essential step of the nitrogen cycle in soil. However, although sunlight is an important environmental factor for soil, the investigation of the influence of sunlight on soil denitrification is limited to plant photosynthesis-mediated processes. Herein, a new pathway, denoted as a biophotoelectrochemical process, which is induced by the direct photoexcitation of soil, was found to greatly enhance soil denitrification. Using red soil as the research object, the soil with irradiation showed nitrate reduction that was 2.6-4.7 times faster than that without irradiation. The irradiation of soil accelerated the reduction of nitrite and enhanced the conversion of nitrous oxide to nitrogen, indicating that more electron sources were generated. This resulted from the photoinduced generation of ferrous substrates and photoelectrons. The contribution of irradiation to soil denitrification was almost half (45.4%), of which 30.9% was from photoinduced ferrous substrates and 14.5% was from photoelectrons. Moreover, a designed biophotoelectrochemical cell provided solid evidence for direct photoelectron transfer from soil photosensitive substrates to microorganisms. Irradiation promoted the enrichment of Alicyclobacillus, which participates in iron oxidation and electroautotrophy. This finding reveals a role of sunlight in soil denitrification that has been thus seriously overlooked and provides solid evidence for the natural occurrence of photoelectrotrophic effects.

Sovleplenib (HMPL-523), a novel Syk inhibitor, for patients with primary immune thrombocytopenia in China: a randomised, double-blind, placebo-controlled, phase 1b/2 study.

BACKGROUND: Spleen tyrosine kinase (Syk) inhibitor is a treatment option for primary immune thrombocytopenia. We aimed to evaluate the safety, tolerability, pharmacokinetics, preliminary activity, and recommended phase 2 dose of sovleplenib in patients with primary immune thrombocytopenia. METHODS: This randomised, double-blind, placebo-controlled, phase 1b/2 study was conducted at nine hospitals in China. Eligible patients were aged 18-75 years, had an ECOG performance score of 0-1, had primary immune thrombocytopenia for more than 6 months, and did not respond or relapsed after previous first-line treatment or had poor response or postoperative relapse after a splenectomy. Dose-escalation (100 mg, 200 mg, or 300 mg given orally once a day) and dose-expansion phases (recommended phase 2 dose) each consisted of an 8-week, double-blind, placebo-controlled period in which patients were randomly assigned (3:1) to receive sovleplenib or placebo with an interactive web response system followed by a 16-week, open-label period with sovleplenib. Patients, investigators, and the sponsor were masked to treatment allocation during the first 8 weeks. The main efficacy endpoint was the proportion of patients whose platelet count reached 30 × 109 platelets per L or higher and was double of the baseline at two consecutive visits during 0-8 weeks without rescue therapy. Efficacy was evaluated by intention-to-treat. This study is registered with ClinicalTrials.gov, NCT03951623. FINDINGS: Between May 30, 2019, and April 22, 2021, 62 patients were assessed for eligibility and 45 (73%) were randomly assigned. Patients received at least one dose of the study drug during the 8-week double-blind period (placebo [n=11] and sovleplenib 100 mg [n=6], 200 mg [n=6], 300 mg [n=16], and 400 mg [n=6]; this group was added following the observation of no protocol-specified safety events at the previous doses). All participants were Asian; 18 (40%) of 45 were male and 27 (60%) were female. The median age was 40·0 years (IQR 33·0-50·0). Ten (29%) of 34 patients in sovleplenib groups versus five (45%) of 11 in the placebo group received concomitant anti-primary immune thrombocytopenia therapy. The recommended phase 2 dose was determined as 300 mg once a day. The proportion of patients who met the main efficacy endpoint were three (50%; 95% CI 12-88) in the 100 mg group, three (50%; 12-88) in the 200 mg group, ten (63%; 35-85) in the 300 mg group, and two (33%; 4-78) in the 400 mg group compared with one (9%; 0-41) in the placebo group. The overall response rate in the 300 mg group was 80% (16 of 20 who received continuous sovleplenib plus those who crossed over from placebo) and the durable response rate was 31% (11-59; five of 16) in the continuous sovleplenib 300 mg and 75% (19-99; three of four) crossed from placebo to sovleplenib during 0-24 weeks. During the 28-day safety evaluation period, two grade 2 or worse treatment-related treatment-emergent adverse events occurred in the sovleplenib groups (hypertriglyceridaemia and anaemia). During 0-8 weeks, the most frequent treatment-emergent adverse events were an increase in blood lactate dehydrogenase, haematuria, and urinary tract infection (seven [21%] of 34 in sovleplenib groups vs one [9%] of 11 in the placebo group); and occult blood-positive and hyperuricaemia (four [12%] vs three [27%] for each). No fatal treatment-emergent adverse events were recorded. INTERPRETATION: Sovleplenib was well tolerated, and the recommended phase 2 dose showed a promising durable response in patients with primary immune thrombocytopenia, which provides evidence for future investigations. A phase 3 trial is ongoing (NCT05029635) to confirm the efficacy and safety of sovleplenib in patients with primary immune thrombocytopenia. FUNDING: HUTCHMED.

27-gauge microincision vitrectomy surgery compared with 25-gauge microincision vitrectomy surgery on wound closure and need for wound suture and other postoperative parameters in the treatment of vitreoretinal disease: A meta-analysis.

We performed a meta-analysis to evaluate the effect of 27-gauge microincision vitrectomy surgery compared with 25-gauge microincision vitrectomy surgery on wound closure and the need for wound suture and other postoperative parameters in the treatment of vitreoretinal disease. A systematic literature search up to June 2022 was performed and 1264 subjects with the vitreoretinal disease at the baseline of the studies; 562 of them were using the 27-gauge microincision vitrectomy surgery, and 722 were using 25-gauge microincision vitrectomy surgery. Odds ratio (OR), and mean difference (MD) with 95% confidence intervals (CIs) were calculated to assess the effect of 27-gauge microincision vitrectomy surgery compared with 25-gauge microincision vitrectomy surgery on wound closure and the need for wound suture and other postoperative parameters in the treatment of vitreoretinal disease using the dichotomous, and contentious methods with a random or fixed-effect model. The 27-gauge microincision vitrectomy surgery subjects had a significantly lower intraoperative and postoperative wound complication (OR, 6.66; 95% CI, 0.46-0.95, P = .02), and wound suture number (OR, 0.38; 95% CI, 0.20-0.71, P = .002), and best corrected visual acuity (MD, -0.03; 95% CI, -0.05 to -0.001, P = .02) compared with 25-gauge microincision vitrectomy surgery in subjects with vitreoretinal disease. However, 27-gauge microincision vitrectomy surgery subjects had no significant difference in the wound closure time (MD, -8.45; 95% CI, -23.44 to 6.55, P = .27), operation time (MD, 0.85; 95% CI, -1.17 to 2.86, P = .41), intraocular pressure at postoperative day 1 (MD, 0.42; 95% CI, -1.45-2.28, P = .66), primary anatomical success rate (OR, 0.83; 95% CI, 0.42-1.63, P = .58), and central macular thickness (MD, 1.81; 95% CI, -21.76 to 25.37, P = .88) compared to 25-gauge microincision vitrectomy surgery in subjects with vitreoretinal disease. The 27-gauge microincision vitrectomy surgery subjects had a significantly lower intraoperative and postoperative wound complication, wound suture number, and best corrected visual acuity, and no significant difference in the wound closure time, operation time, intraocular pressure at postoperative day 1, primary anatomical success rate, and central macular thickness compared to 25-gauge microincision vitrectomy surgery in subjects with vitreoretinal disease. The analysis of outcomes should be with caution because of the low sample size of 12 out of 15 studies in the meta-analysis and a low number of studies in certain comparisons.

Flower-like molybdenum disulfide/cobalt ferrite composite for the extraction of benzotriazole UV stabilizers in environmental samples.

Benzotriazole UV stabilizers (BUVSs) are a class of emerging contaminants of concern; the development of rapid and convenient monitoring method for these trace-level pollutants in waters is of crucial significance in environmental science. Here, a novel magnetic flower-like molybdenum disulfide/cobalt ferrite nanocomposite (MoS2/CoFe2O4) was synthesized by hydrothermal reaction. Compared with the conventional Fe3O4-based magnetic composites, the proposed material just required a minimum consumption of Co/Fe towards the equivalent of MoS2 while providing superior magnetization performance. Taking advantages of high adsorption capacity, extraordinary stability, and repeatability in construction, MoS2/CoFe2O4 was applied to the extraction to BUVSs. The enrichment factors of three BUVSs were in the range 164-193 when 20 mL of environmental water sample was loaded on 40 mg of the adsorbent. MoS2/CoFe2O4 could be regenerated and recycled at least 10 cycles of adsorption/desorption with recoveries of 80.1-111%. The method of MoS2/CoFe2O4-based extraction coupled with high-performance liquid chromatography-variable wavelength detector was applied to the monitoring of BUVSs in seawater, lake water, and wastewater, which gave detection limits (S/N = 3) of 0.023-0.030 ng·mL-1 and recoveries of 80.1-110%. The intra-day and inter-day precisions (relative standard deviation, RSDs, n = 3) were in the range 1.6-7.5% and 3.2-11.5%, respectively. The approach is an alternative for efficient and sensitive extraction and determination of trace-level environmental pollutants in waters.

UV-dependent freshwater effect factor of nanoscale titanium dioxide for future life cycle assessment application.

Environmental impacts of nanoscale titanium dioxide (TiO2 ) should be assessed throughout the lifetime of nanoparticles (NPs) to improve the state of knowledge of the overall sustainability. Life cycle assessment (LCA) has been previously recognized as a promising approach to systematically evaluating environmental impacts of NPs. As a result of their unique nanospecific properties, characterization factors (CF) were previously used for compensating the release and potential impacts of TiO2 NPs. However, because TiO2 NPs are known to generate reactive oxygen species and elicit toxicity to freshwater organisms, the lack of adequate UV-dependent effect factors (EFs) remains a major shortcoming when addressing their life cycle impacts. To complement the LCA of TiO2 -NPs-enabled products under their specific applications, we recapitulated the freshwater toxicity of TiO2 NPs and then modeled in USEtox to determine trophic level EF ranges under UV and non-UV exposure conditions. Results indicate that EFs derived for non-UV exposure were 52 (42.9-65) potentially affected fraction (PAF) m3 /kg, and combined toxicity data derived EFs were 70.1 (55.6-90.5) PAF m3 /kg. When considering only the UV-induced exposure condition, the modeled EF increased to 500 (333-712) PAF m3 /kg. Our work highlights that case-dependent EFs should be considered and applied to reflect more realistic ecological impacts and illustrate comprehensive life cycle environmental impacts for nanoenabled products. Integr Environ Assess Manag 2023;19:578-585. © 2022 SETAC.

Identification of a novel sepsis prognosis model and analysis of possible drug application prospects: Based on scRNA-seq and RNA-seq data.

Sepsis is a disease with a high morbidity and mortality rate. At present, there is a lack of ideal biomarker prognostic models for sepsis and promising studies using prognostic models to predict and guide the clinical use of medications. In this study, 71 differentially expressed genes (DEGs) were obtained by analyzing single-cell RNA sequencing (scRNA-seq) and transcriptome RNA-seq data, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment pathway analyses were performed on these genes. Then, a prognosis model with CCL5, HBD, IFR2BP2, LTB, and WFDC1 as prognostic signatures was successfully constructed after univariate LASSO regression analysis and multivariate Cox regression analysis. Kaplan-Meier (K-M) survival analysis, receiver operating characteristic (ROC) time curve analysis, internal validation, and principal component analysis (PCA) further validated the model for its high stability and predictive power. Furthermore, based on a risk prediction model, gene set enrichment analysis (GSEA) showed that multiple cellular functions and immune function signaling pathways were significantly different between the high- and low-risk groups. In-depth analysis of the distribution of immune cells in healthy individuals and sepsis patients using scRNA-seq data revealed immunosuppression in sepsis patients and differences in the abundance of immune cells between the high- and low-risk groups. Finally, the genetic targets of immunosuppression-related drugs were used to accurately predict the potential use of clinical agents in high-risk patients with sepsis.

Meta-Analysis of Long-Term Efficacy of Proliferative Diabetic Retinopathy Based on Intelligent Medical Treatment.

In order to solve some problems of subhealth and high chronic diseases, the diagnosis and treatment of value-added diabetic retinopathy are studied. In particular, diabetes, a high chronic disease, poses a great threat to people's health. With the continuous improvement of national health awareness, the medical field also begins to pay more attention to the diagnosis and treatment of value-added diabetic retinopathy. In order to improve the long-term treatment of value-added diabetic retinopathy through intelligent medical monitoring and systematic scientific efficacy analysis and evaluation, the purpose of this study is to explore how to effectively achieve the meta-analysis of long-term efficacy of proliferative diabetic retinopathy through intelligent medical treatment. Through the study of diabetic retinopathy, the system can help doctors to achieve unlimited further signs of parameter acquisition and transmission and build more mature after treatment of the results of the monitoring platform. At the same time, a conclusion based on vitrectomy was proposed to effectively improve the surgical efficacy of patients with proliferative diabetic retinopathy.

Shenxian-Shengmai Oral Liquid Evoke Autophagy of Fibroblast to Attenuate Sinoatrial Node Fibrosis in Sick Sinus Syndrome Mice via the AKT/mTOR Pathway.

Sick sinus syndrome (SSS) is closely associated with cardiac syncope and sudden death, wherein sinoatrial node (SAN) fibrosis is one of the main pathological changes that occur. Shenxian-Shengmai oral liquid (SXSM) has been clinically proven to significantly improve the heart rate of SSS patients. In this study, we aimed to explore the mechanism of SXSM in reducing the SAN fibrosis by combining in vitro and in vivo experiments. Accordingly, the SSS model was constructed by slowly pumping angiotensin II (AngII) with a micro-osmotic pump. The degree of fibrosis was evaluated by Masson's trichrome staining and immunofluorescence staining of the fibrosis marker protein. In addition, NIH-3T3 mouse fibroblasts were used to simulate SAN fibroblasts to further explore the mechanism, with AngII used as the cellular fibrosis inducer. Monodansylcadaverine (MDC) staining and transmission electron microscopy were employed to assay the autophagy content, whereas immunofluorescence staining and Western blotting were employed to elucidate the related protein expression. Finally, fibroblasts were given the AKT phosphorylation agonist SC79 to reversely verify the effects of SXSM. The results showed that SXSM could significantly increase the heart rate of SSS mice by reducing the deposition of extracellular matrix (ECM) in SAN induced by AngII. According to in vivo experiments, when compared with the model group, SSS mice treated with SXSM developed less fibrosis in the SAN area. In vitro experiments revealed that AngII could restrain autophagy by activating the phosphorylation of the AKT/mTOR pathway, thereby increasing the deposition of ECM. Moreover, SXSM pretreatment prevented this upregulation. After the intervention of SC79, the protective effect of SXSM was weakened. In conclusion, SXSM activated autophagy through the AKT/mTOR pathway, which in turn reduced the deposition of the ECM in SAN induced by AngII, attenuated the fibrosis of SAN, and improved the decreased heart rate in the SSS mice.

NRF-2/HO-1 Pathway-Mediated SHOX2 Activation Is a Key Switch for Heart Rate Acceleration by Yixin-Fumai Granules.

Population aging has led to increased sick sinus syndrome (SSS) incidence; however, no effective and safe medical therapy has been reported thus far. Yixin-Fumai granules (YXFMs), a Chinese medicine granule designed for bradyarrhythmia treatment, can effectively increase SSS patients' heart rate. Senescence-induced sinoatrial node (SAN) degeneration is an important part of SSS pathogenesis, and older people often show high levels of oxidative stress; reactive oxygen species (ROS) accumulation in the SAN causes abnormal SAN pacing or conduction functions. The current study observed the protective effects of YXFMs on senescent SAN and explored the relationship between the NRF-2/HO-1 pathway, SHOX2, and T-type calcium channels. We selected naturally senescent C57BL/6 mice with bradycardia to simulate SSS; electrocardiography, Masson's trichrome staining, and DHE staining were used to assess SAN function and tissue damage. Immunofluorescence staining and Western blotting were used to assay related proteins. In vitro, we treated human-induced pluripotent stem cell-derived atrial myocytes (hiPSC-AMs) and mouse atrial myocyte-derived cell line HL-1 with D-galactose to simulate senescent SAN-pacemaker cells. CardioExcyte96 was used to evaluate the pulsatile function of the hiPSC-AMs, and the mechanism was verified by DCFH-DA, immunofluorescence staining, RT-qPCR, and Western blotting. The results demonstrated that YXFMs effectively inhibited senescence-induced SAN hypofunction, and this effect possibly originated from scavenging of ROS and promotion of NRF-2, SHOX2, and T-type calcium channel expression. In vitro experiment results indicated that ML385, si-SHOX2, LDN193189, and Mibefradil reversed YXFMs' effects. Moreover, we, for the first time, found that ROS accumulation may hinder SHOX2 expression; YXFMs can activate SHOX2 through the NRF-2/HO-1 pathway-mediated ROS scavenging and then regulate CACNA1G through the SHOX2/BMP4/GATA4/NKX2-5 axis, improve T-type calcium channel function, and ameliorate the SAN dysfunction. Finally, through network pharmacology and molecular docking, we screened for the most stable YXFMs compound that docks to NRF-2, laying the foundation for future studies.

The synergistic effect of CDKN2B-AS1 and SPC25 on triple-negative breast cancer.

Background: Accumulating evidence suggests that long non-coding ribonucleic acid (RNA) cyclin-dependent kinase inhibitor 2B antisense RNA 1 (CDKN2B-AS1) and messenger RNA (mRNA) spindle component 25 (SPC25) contribute to tumorigenesis and progression in various cancers. However, the synergistic effect between CDKN2B-AS1 and SPC25 has not yet been fully elucidated in triple-negative breast cancer (TNBC). This study sought to examine the synergistic effect of CDKN2B-AS1 and SPC25 and uncover a novel mechanism for the progression of TNBC. Methods: The transcriptome profiles of TNBC in The Cancer Genome Atlas (TCGA) were calculated for differentially expressed genes (DEGs). Gene co-expression networks were constructed via a weighted correlation network analysis. We validated the relationship between CDKN2B-AS1 and SPC25 by bioinformatics and in-vitro studies (including Cell Counting Kit-8, transwell assays, and quantitative real-time polymerase chain reaction). Results: CDKN2B-AS1 was found to be carcinogenic and was significantly upregulated and co-expressed with elevated SPC25 expression levels in the TNBC cells and sequencing profiles. Notably, the SPC25 mRNA levels were associated with poor clinical outcomes in TNBC patients. Specifically, the knockdown of CDKN2B-AS1 significantly inhibited TNBC cell proliferation and migration. Conclusions: We identified a novel cancer-promoting regulation axis. The co-expression of CDKN2B-AS1 and SPC25 is expected to serve as a powerful candidate biomarker for diagnostic and prognostic purposes in TNBC.